The novel and useful present invention is summarized by two points that an excellent organic molecular catalyst which has been unknown is found and a certain asymmetric reactions which have been difficult to practically apply is efficiently realized using the organic molecular catalysts. The following will describe conventional technologies with regard to the respective points.
Compounds useful per se, e.g., pharmaceuticals, pesticides, veterinary medicines, functional molecules, and new material compounds, frequently contain asymmetric carbons and the efficient construction thereof belongs a category of problem which is most important and requires the highest production technique among recent problems in synthetic organic chemistry. As one of methods for efficiently constructing the asymmetric carbons during processes for producing the useful compounds per se, it is general to use asymmetric reactions. For the ultimate purpose of enhancing the efficiency as far as possible, a large number of organometallic catalysts have been recently molecularly designed and produced, and excellent usefulness thereof has been proved as described in J. Am. Chem. Soc., 123, 2907-2908, 2001 and Angew. Chem. Int. Ed., 42, 2144-2147, 2003. However, it cannot be said that the asymmetric reactions using the organometallic catalysts contain no problem. Namely, in the case when a step of using an organometallic catalyst is incorporated into the production of a final product or an intermediate, a minute amount of the metal remains in the final product and the complete elimination of the metal sometimes heightens the technical hurdle of production and purification of the product. Moreover, in the case when an asymmetric reaction is repeatedly carried out using an organometallic catalyst, it is sometimes observed that chemical yields or asymmetric yields decrease while the reaction is repeated. The above are problems in the application of organometallic catalysts to asymmetric reactions.
The following will describe the technologies for efficiently production of useful compounds per se, e.g., pharmaceuticals, pesticides, veterinary medicines, functional molecules, and new material compounds, or important synthetic intermediates for producing useful compounds. As the technologies, various asymmetric reactions have been reported, and recently a novel carbon-carbon bond-forming reaction wherein a substrate containing a nitrogen atom is involved as described in Chem. Commun., 2001, 1876-1877 and Eur. J. Org. Chem., 2002, 696-701. The reaction initially called “the Baylis-Hillman reaction of imine” at the time when it was found was at first not necessarily said to be as an excellent asymmetric reaction. However, thereafter, an asymmetric reaction has been achieved using an organic molecular catalyst derived from a natural product having asymmetry. Currently, production examples wherein asymmetric yields of 90% or more at maximum are realized by Shi et. al have been reported as described in Angew. Chem. Int. Ed., 41, 4507-4510, 2002 and Chem. Commun., 2003, 1310-1311 and thus the “aza-Baylis-Hillman reaction” as an asymmetric reaction has been acknowledged.
However, the asymmetric yields in the aza-Baylis-Hillman reaction have been achieved using organic molecular catalysts derived from natural products and the reaction contains not necessarily no problem as a technology for producing useful compounds per se, e.g., pharmaceuticals, pesticides, veterinary medicines, functional molecules, and new material compounds, or important synthetic intermediates for producing useful compounds. Namely, for the efficient production of useful compounds or important synthetic intermediates for producing the same, it is required a technology capable of freely constructing an asymmetric carbon which has a necessary stereochemistry, in other words, an efficient method capable of constructing any asymmetric center. As the most recent example of asymmetric reactions in this field, an asymmetric aza-Baylis-Hillman reaction using an organic molecular catalyst which has a binaphthyl skeleton has been reported by Shi et al. as described in Chem. Commun., 2003, 1310-1311. However, any efficient application example capable of simultaneously realizing a high asymmetric yield of 90% or more and a practical chemical yield of 90% or more has not been known in the above reaction. Problems of the use of the aza-Baylis-Hillman reaction at the industrial construction of an asymmetric carbon are described above.